The temporal origin of dentate granule neurons dictates their role in spatial memory

Abstract

The dentate gyrus is one of the only brain regions that continues its development after birth in rodents. Adolescence is a very sensitive period during which cognitive competences are programmed. We investigated the role of dentate granule neurons (DGNs) born during adolescence in spatial memory and compared them with those generated earlier in life (in embryos or neonates) or during adulthood by combining functional imaging, retroviral and optogenetic tools to tag and silence DGNs. By imaging DGNs expressing Zif268, a proxy for neuronal activity, we found that neurons generated in adolescent rats (and not embryos or neonates) are transiently involved in spatial memory processing. In contrast, adult-generated DGNs are recruited at a later time point when animals are older. A causal relationship between the temporal origin of DGNs and spatial memory was confirmed by silencing DGNs in behaving animals. Our results demonstrate that the emergence of spatial memory depends on neurons born during adolescence, a function later assumed by neurons generated during adulthood.

Adult-born dentate granule cells promote hippocampal population sparsity

“…Thus, mature abDGCs do not reproduce the local circuit wiring sculpted during development, in line with recent work showing that mature abDGCs exhibit distinct morphological features compared with developmentally born neurons 57,58 . Together with work showing that the temporal origin of developmental DG cells determines single-neuron properties 59,60 , these findings converge to the view that the adult DG hosts a heterogeneous population of granule cells 61 . This heterogeneity could be central to the network's ability to diversify population responses and support hippocampal functions.…”

ΔFosB accumulation in hippocampal granule cells drives cFos pattern separation during spatial learning

“…Thus, DG cFos expression and overlap are strongly driven in the WM regardless of training level (ET vs OT) or difficulty of the task (OT vs RT), consistent with the concept that the hippocampus is highly engaged in spatial navigation tasks and that very different environments activate non-overlapping ensembles. cFos + neurons in DG participate in spatial memory recall days later Lesion 31,32 and optogenetic manipulation [33][34][35][36] experiments indicate that the DG plays a role in spatial memory acquisition and recall. However, those experiments did not address if particular memories are encoded by a specific subset or ensemble of neurons in the DG (engram cells).…”

cFos ensembles in the dentate gyrus rapidly segregate over time and do not form a stable map of space

“…2), consistent with the concept that the hippocampus is highly engaged in spatial navigation tasks. cFos + neurons in DG participate in spatial memory recall days later Lesion 30,31 and optogenetic manipulation [32][33][34][35] experiments indicate that the DG plays a role in spatial memory acquisition and recall. However, these experiments did not address if those particular memories are encoded by a specific subset or ensemble of neurons in the DG ("engram cells").…”